Mark Woodhead

Central Manchester University Hospitals NHS Foundation Trust, Manchester, England, United Kingdom

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Publications (70)455.57 Total impact

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    ABSTRACT: A matched-propensity analysis of national data from the British Thoracic Society community-acquired pneumonia audit was conducted (n=13 725). Overall, time to first antibiotic (TFA) was ≤4 h in 63%. Adjusted 30-day inpatient (IP) mortality was lower for adults with TFA ≤4 h compared with TFA >4 h (adjusted OR 0.84, 95% CI 0.74 to 0.94; p=0.003). Increasing TFA was associated with greater OR of 30-day IP mortality (p value for trend=0.001), but no TFA threshold was evident. Although we found an association between TFA and mortality, we cannot say whether this is causal or whether TFA might just be a quality measure for overall or other processes of care.
    No preview · Article · Nov 2015 · Thorax
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    ABSTRACT: Lower respiratory tract infections frequently complicate stroke and adversely affect outcome. There is currently no agreed terminology or gold-standard diagnostic criteria for the spectrum of lower respiratory tract infections complicating stroke, which has implications for clinical practice and research. The aim of this consensus was to propose standardized terminology and operational diagnostic criteria for lower respiratory tract infections complicating acute stroke. Systematic literature searches of multiple electronic databases were undertaken. An evidence review and 2 rounds of consensus consultation were completed before a final consensus meeting in September 2014, held in Manchester, United Kingdom. Consensus was defined a priori as ≥75% agreement between the consensus group members. Consensus was reached for the following: (1) stroke-associated pneumonia (SAP) is the recommended terminology for the spectrum of lower respiratory tract infections within the first 7 days after stroke onset; (2) modified Centers for Disease Control and Prevention (CDC) criteria are proposed for SAP as follows-probable SAP: CDC criteria met, but typical chest x-ray changes absent even after repeat or serial chest x-ray; definite SAP: CDC criteria met, including typical chest x-ray changes; (3) there is limited evidence for a diagnostic role of white blood cell count or C-reactive protein in SAP; and (4) there is insufficient evidence for the use of other biomarkers (eg, procalcitonin). Consensus operational criteria for the terminology and diagnosis of SAP are proposed based on the CDC criteria. These require prospective evaluation in patients with stroke to determine their reliability, validity, impact on clinician behaviors (including antibiotic prescribing), and clinical outcomes. © 2015 American Heart Association, Inc.
    Full-text · Article · Jun 2015 · Stroke
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    ABSTRACT: C21 CONFLICT OR PEACEFUL CO-EXISTENCE? THE BACTERIAL LUNG MICROBIOME AND HOST IMMUNITY / Poster Discussion Session / Tuesday, May 19/9:30 AM-11:30 AM / Mile High Ballroom 1 A-B (Lower Level) Colorado Convention Center The Genus Haemophilus Was Dominant In A Cohort With Community Acquired Pneumonia And Low Species Diversity Was Related To Age And Prior Pulmonary Disease D. G. Wootton1, M. J. Cox2, G. L. Hickey3, O. Eneje4, J. Court4, 5, L. Macfarlane4, S. Wilks4, M. Woodhead6, W. O. Cookson2, M. F. Moffatt2, P. J. Diggle3, S. B. Gordon4 University of Liverpool, Liverpool, United Kingdom, 2Imperial College London, 6LY, United Kingdom, University of Liverpool, 7BE, United Kingdom, 4Liverpool School of Tropical Medicine, 5QA, United Kingdom, 5, 6Central Manchester University Hospitals NHS Foundation Trust, 9WM, United Kingdom Corresponding author's email: dwootton@liverpool.ac.uk Rationale The causative organism(s) responsible for the syndrome of community acquired pneumonia (CAP) are frequently not defined. Culture-independent techniques offer the possibility of new insights into the range and interactions of pathogens in CAP. Here we explored the bacteria present in sputum from patients with CAP by 16SrRNA gene sequencing. Methods Between February 2011 and March 2013, and as part of a prospective observational cohort study, CAP admissions were recruited within 24 hours of admission at two hospitals in Liverpool. Eligibility criteria were:- Aged ≥ 16yrs; Treatment for CAP (British Thoracic Society in-hospital definition) Exclusion Criteria were:- Admission within the last 14 days; Bronchiectasis or cystic fibrosis; Immunocompromised Self-expectorated sputum was frozen at -80oC in sealed, gamma irradiated pots with no prior processing. DNA was extracted using FastDNATM extraction kits and a bead-beater. Pooled, barcoded products from quadruplicate PCRs of the V3-5 region of the 16SrRNA gene were sequenced using the Roche 454FLX platform. Compositional analysis of relationships between individual taxa and clinical variables was performed using the R package ALDeX2. Bacterial species diversity was explored with the R package Phyloseq. Results 169 subjects provided 86 acute sputum samples of which 76 were analysed (44.7% women, median age 68.5yrs (IQR 49 – 76), median CURB65 score 2 (IQR 0-2.25), median pro-calcitonin 0.73 ng/ml (IQR 0.18-4.30), median length of stay 5 days (IQR 2.75 – 7.25)). Although several individual bacterial operational taxonomic units (OTUs) appeared to be associated with clinical parameters none were significant after correction for multiple testing (Benjamini-Hochberg method). Following rarefaction to 549 reads and removal of singletons, 774 OTUs were identified across all sputum samples; median per-sample was 43 (IQR 23-62). Multiple-regression revealed age (P=0.014) and underlying pulmonary disease (P=0.006) were independently associated with the diversity (Shannon) of bacterial species in a subject’s sputum. Haemophilus_617 was the most abundant OTU in these samples (Figure). Image.png Conclusions In this cohort of patients with CAP, increasing age and underlying pulmonary disease were associated with lower bacterial species diversity. These are well documented risk factors for CAP and are associated with worse outcomes. In culture-based studies pneumococcus is the most commonly implicated bacterial pathogen in CAP. In this study streptococcal OTUs were amongst the most abundant but Haemophilus_617 was twice as abundant. This raises the possibility that bacteria of the genus Haemophilus may be more important than has previously been thought in the context of CAP. This abstract is funded by: This work was supported by a Doctoral Research Fellowship awarded to D.Wootton by the UK National Institute of Health Research (NIHR) and by the Wellcome Trust. Am J Respir Crit Care Med 191;2015:A3954 Internet address: www.atsjournals.org Online Abstracts Issue
    Full-text · Conference Paper · May 2015
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    ABSTRACT: Diagnosis of pneumonia complicating stroke is challenging, and there are currently no consensus diagnostic criteria. As a first step in developing such consensus-based diagnostic criteria, we undertook a systematic review to identify the existing diagnostic approaches to pneumonia in recent clinical stroke research to establish the variation in diagnosis and terminology. Studies of ischemic stroke, intracerebral hemorrhage, or both, which reported occurrence of pneumonia from January 2009 to March 2014, were considered and independently screened for inclusion by 2 reviewers after multiple searches using electronic databases. The primary analysis was to identify existing diagnostic approaches for pneumonia. Secondary analyses explored potential reasons for any heterogeneity where standard criteria for pneumonia had been applied. Sixty-four studies (56% ischemic stroke, 6% intracerebral hemorrhage, 38% both) of 639 953 patients were included. Six studies (9%) reported no information on the diagnostic approach, whereas 12 (19%) used unspecified clinician-reported diagnosis or initiation of antibiotics. The majority used objective diagnostic criteria: 20 studies (31%) used respiratory or other published standard criteria; 26 studies (41%) used previously unpublished ad hoc criteria. The overall occurrence of pneumonia was 14.3% (95% confidence interval 13.2%-15.4%; I(2)=98.9%). Occurrence was highest in studies applying standard criteria (19.1%; 95% confidence interval 15.1%-23.4%; I(2)=98.5%). The substantial heterogeneity observed was not explained by stratifying for other potential confounders. We found considerable variation in terminology and the diagnostic approach to pneumonia. Our review supports the need for consensus development of operational diagnostic criteria for pneumonia complicating stroke. © 2015 American Heart Association, Inc.
    Full-text · Article · Apr 2015 · Stroke
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    ABSTRACT: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic. Multicentre, pragmatic, blinded, randomised placebo-controlled trial. Thirty to 40 hospitals in the UK. Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies. Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.
    Full-text · Article · Feb 2015 · Health technology assessment (Winchester, England)
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    ABSTRACT: Objective To determine the association between 30-day inpatient mortality and route of admission to hospital, for adults with community acquired pneumonia (CAP). Methods We studied 16 313 adults included in the British Thoracic Society (BTS) national CAP audit dataset. Comparisons were made between adults admitted via emergency departments (ED) with non-ED routes of admission, with regard to 30-day inpatient mortality. Secondary outcome measures were adherence to national CAP guidelines (time to first chest X-ray ≤4 h from admission; time to first antibiotic dose ≤4 h from admission; antibiotic choice; and antibiotic route of administration) by route of admission. Results Of adults hospitalised with CAP, 75.6% were admitted via ED; these adults had a greater prevalence of comorbid illness and higher disease severity in comparison with non-ED admissions. Adjusted 30-day inpatient mortality was similar for ED versus non-ED route of admission (OR 1.10, 95% CI 0.96 to 1.25). Admissions via ED were associated with faster processes of care (time to chest X-ray ≤4 h, adjusted OR 3.39, 95% CI 2.79 to 4.12; time to first antibiotic ≤4 h, adjusted OR 1.62, 95% CI 1.42 to 1.84) and greater use of intravenous antibiotics regardless of disease severity (adjusted OR 1.58, 95% CI 1.43 to 1.74). Conclusions Adults with CAP admitted via EDs have more comorbid illness and greater disease severity compared to those admitted via non-ED routes. Following adjustment for these differences, 30-day inpatient mortality was not associated with route of admission.
    No preview · Article · Dec 2014 · Emergency Medicine Journal
  • Sinan Eccles · Celia Pincus · Bernard Higgins · Mark Woodhead

    No preview · Article · Dec 2014 · BMJ Clinical Research
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    Giovanni Sotgiu · Mark Woodhead

    Preview · Article · Jul 2014 · European Respiratory Journal
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    D. G. Wootton · P. J. Diggle · M. Woodhead · S. B. Gordon
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    ABSTRACT: D. G. Wootton , P. J. Diggle , M. Woodhead , S. B. Gordon Liverpool School of Tropical Medicine, Liverpool, United Kingdom, , University of Liverpool, Institute of Infection and Global Health, Liverpool, United Kingdom, Manchester Royal Infirmary, Manchester, United Kingdom Corresponding author's email: dwootton@liverpool.ac.uk Rationale Despite evidence of excess long term morbidity and mortality, little is known about the factors that affect rates of recovery from community acquired pneumonia (CAP). One mechanism that may account for differential resolution of inflammation and associated symptoms is efferocytosis. This process of removing apoptotic host cells is a vital component of recovery from acute inflammation and is impaired in a number of inflammatory lung conditions. We measured efferocytosis in patients recovering from CAP and looked for factors that influenced this process. Methods As part of a prospective observational cohort study, between February 2011 and 31 March 2013, at two hospitals in Liverpool (UK), st admissions were recruited within 24 hours of admission. Eligibility criteria were: · Aged ≥ 16 · Treatment for CAP (British Thoracic Society in hospital definition). Exclusion Criteria were:-· Admission within the last 14 days · Bronchiectasis or cystic fibrosis · Immunocompromised One month following admission, subjects were invited to re-visit for bronchoscopy and bronchoalveolar lavage (BAL). Saline was instilled into the middle lobe and alveolar macrophages were separated and cultured. Simultaneously, whole blood was taken from the subject and neutrophils were separated, stained green and allowed to become apoptotic by culture for 20 hours. The neutrophils were added to the macrophages and co-cultured for 90 minutes. Efferocytosis was then measured using flow cytometry. Results 169 subjects (48% women, mean age 64y-range 16-94y) were recruited. 22 volunteered to undergo research bronchoscopy (36% women, mean age 48 – range 22-82y). Multiple regression analysis of these 22 subjects revealed smoking (p<0.001) and prior statin use (p<0.001) as having significant associations with efferocytosis. The analysis used a linear mixed effects model to account for inter-subject and intra-subject efferocytosis assay variation. Inter-subject and intra-subject (assay) variation accounted for 84.3% and 15.7%, respectively of the variation in the data. efferocytosis mean and statin.jpg Conclusions These experiments demonstrate that, in patients recovering from CAP, there is a statistically significant association between smoking, prior statin use and the capacity of alveolar macrophages to carry out efferocytosis. These observations have not been made previously in patients recovering from pneumonia. However, previous studies have shown that the reduced capacity for efferocytosis in alveolar macrophages from subjects with COPD can be increased by exposure to statins. Ours was a small study but the data support the epidemiological association between statin use and improved outcomes following CAP and suggest efferocytosis is one possible mechanism to explain this. This abstract is funded by: This work was supported by a Doctoral Research Fellowship awarded to Dr D.G. Wootton by National Instituteof Health Research (NIHR)UK. Am J Respir Crit Care Med 189;2014:A5237 Internet address: www.atsjournals.org Online Abstracts Issue
    Full-text · Conference Paper · May 2014
  • Mark Woodhead
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    ABSTRACT: Angiotensin converting enzyme inhibitors (ACEIs) and statins have been identified to have possible beneficial effects in the management of pneumonia. ACEIs have been shown to increase cough and reduce dysphagia-two mechanisms that could reduce susceptibility to pneumonia. Studies have found a reduction in pneumonia incidence in those taking ACEIs however overall benefit remains unproven. The reason for this is that studies have only been conducted in those with risk factors requiring ACEI treatment. Statins have multiple cellular effects that could be beneficial in pneumonia. Benefit in animal studies has been shown. While associations between statin use and both reduced pneumonia incidence and better outcomes have been found the results are not consistent between studies and a causal effect has not been proven. Randomised controlled trials in the general population, with pneumonia as an endpoint, are required for both ACEIs and statins to determine whether beneficial effects from such treatments in pneumonia occur.
    No preview · Article · Apr 2014 · Turk Toraks Dergisi
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    Mark Woodhead

    Preview · Article · Feb 2014 · European Respiratory Journal
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    ABSTRACT: Tuberculosis (TB) incidence is rising globally, with drug resistance becoming increasingly problematic. Microbiological confirmation ensures correct anti-tuberculous chemotherapy. We retrospectively analysed all TB cases diagnosed in Central Manchester in 2009 investigating how often we are not achieving microbiological diagnosis, factors influencing this and whether opportunities to obtain microbiological samples are missed. 128/156 (82%) cases had samples sent for microbiology. Factors affecting this included disease site, with ocular disease least likely to be sampled (p < 0.0001), and patient age (with children less likely to be sampled p = 0.002). Ethnicity did not affect sampling (n.s.). Overall, 92/156 (59%) cases were culture positive. Negative culture was related to specimen type (p < 0.0001) and patient age (p = 0.019), with children significantly less likely to have a positive culture. Ethnicity and disease site did not affect culture results. There was a trend towards culture positivity being more common in pulmonary (75%) than non-pulmonary (46%) disease (n.s.). In only 7 (4%), could samples have been sent where they were originally absent (3) or further samples obtained where the cultures proved to be negative (4). Despite an overall culture positive rate of 59%, opportunities to achieve microbiological confirmation are seldom missed. In our centre, which is typical of UK practice, this lack of capacity to increase microbiological confirmation, particularly in an era of increasing importance of extra-pulmonary TB, is concerning. Improvements in sample acquisition and laboratory methods are urgently required.
    No preview · Article · Oct 2013 · Respiratory medicine
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    Waseem Asrar Khan · Mark Woodhead
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    ABSTRACT: This article is a non-systematic review of selected recent publications in community-acquired pneumonia, including a comparison of various guidelines. Risk stratification of patients has recently been advanced by the addition of several useful biomarkers. The issue of single versus dual antibiotic treatment remains controversial and awaits a conclusive randomized controlled trial. However, in the meantime, there is a working consensus that more severe patients should receive dual therapy.
    Preview · Article · Oct 2013 · F1000 Prime Reports
  • Mark Woodhead

    No preview · Article · Sep 2013 · Thorax
  • Philip A J Crosbie · Mark Woodhead

    No preview · Article · May 2013 · Thorax
  • Mark Woodhead · Ruth Wiggans

    No preview · Article · Feb 2013 · Expert Review of Respiratory Medicine
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    ABSTRACT: The benefits of β-lactam/macrolide combination therapy over β-lactam therapy alone for the treatment of hospitalised community-acquired pneumonia (CAP) in relation to pneumonia severity are uncertain. We studied 5240 adults hospitalised with CAP from 72 secondary care trusts across England and Wales. The overall 30-day inpatient (IP) death rate was 24.4%. Combination therapy was prescribed in 3239 (61.8%) patients. In a multivariable model, combination therapy was significantly associated with lower 30-day IP death rate in patients with moderate-severity CAP (adjusted OR 0.54, 95% CI 0.41 to 0.72) and high-severity CAP (adjusted OR 0.76, 95% CI 0.60 to 0.96) but not low-severity CAP.
    No preview · Article · Oct 2012 · Thorax
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    Wei Shen Lim · Mark Woodhead

    Preview · Article · Sep 2012 · Thorax
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    ABSTRACT: Patients with Chronic Obstructive Pulmonary Disease (COPD) are at higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the general population. However, no studies have been performed in general practice assessing longitudinal incidence rates for CAP in COPD patients or risk factors for pneumonia onset. A cohort of COPD patients aged ≥ 45 years, was identified in the General Research Practice Database (GPRD) between 1996 and 2005, and annual and 10-year incidence rates of CAP evaluated. A nested case-control analysis was performed, comparing descriptors in COPD patients with and without CAP using conditional logistic regression generating odds ratios (OR) and 95% confidence intervals (CI). The COPD cohort consisted of 40,414 adults. During the observation period, 3149 patients (8%) experienced CAP, producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92% of patients with pneumonia diagnosis had suffered only one episode. Multivariate modelling of pneumonia descriptors in COPD indicate that age over 65 years was significantly associated with increased risk of CAP. Other independent risk factors associated with CAP were co-morbidities including congestive heart failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6) were also significantly associated with risk of CAP. COPD patients presenting in general practice with specific co-morbidities, severe COPD, and age >65 years are at increased risk of CAP.
    Full-text · Article · May 2012 · Respiratory medicine
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    Paul A Marsden · Mark Woodhead

    Preview · Article · Mar 2012 · Primary care respiratory journal: journal of the General Practice Airways Group

Publication Stats

3k Citations
455.57 Total Impact Points

Institutions

  • 2012-2015
    • Central Manchester University Hospitals NHS Foundation Trust
      Manchester, England, United Kingdom
  • 2009-2015
    • The University of Manchester
      • Respiratory Medicine Research Group
      Manchester, England, United Kingdom
  • 2011
    • British Thoracic Society
      United Kingdom
  • 1991
    • St George's, University of London
      Londinium, England, United Kingdom
  • 1989
    • Saint James School Of Medicine
      Παρκ Ριτζ, Illinois, United States
  • 1986
    • Nottingham University Hospitals NHS Trust
      Nottigham, England, United Kingdom